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Metabolites 2019, 9(3), 47; https://doi.org/10.3390/metabo9030047

Defining Metabolic Rewiring in Lung Squamous Cell Carcinoma

1
Aberystwyth University, Institute of Biological, Environmental and Rural Sciences (IBERS), Ceredigion SY23 3DA, UK
2
São Paulo State University (UNESP), Faculty of Medicine, Dept. of Surgery and Orthopedics, Botucatu 18618687, Brazil
3
São Paulo State University (UNESP), Experimental Research Unity (UNIPEX), Botucatu 18618687, Brazil
4
São Paulo State University (UNESP), School of Veterinary Medicine and Animal Science, Dept. of Veterinary Clinic, Botucatu 18618687, Brazil
5
Clinical Research Centre, Prince Philip Hospital, Hywel Dda University Health Board, Wales SA14 8QF, UK
6
School of Medicine, Swansea University, Singleton Park, Swansea, Wales SA2 8PP, UK
*
Authors to whom correspondence should be addressed.
Received: 8 February 2019 / Revised: 26 February 2019 / Accepted: 2 March 2019 / Published: 7 March 2019
(This article belongs to the Special Issue Cancer Metabolomics 2019)
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PDF [9836 KB, uploaded 7 March 2019]
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Abstract

Metabolomics based on untargeted flow infusion electrospray ionization high-resolution mass spectrometry (FIE-HRMS) can provide a snap-shot of metabolism in living cells. Lung Squamous Cell Carcinoma (SCC) is one of the predominant subtypes of Non-Small Cell Lung Cancers (NSCLCs), which usually shows a poor prognosis. We analysed lung SCC samples and matched histologically normal lung tissues from eight patients. Metabolites were profiled by FIE-HRMS and assessed using t-test and principal component analysis (PCA). Differentially accumulating metabolites were mapped to pathways using the mummichog algorithm in R, and biologically meaningful patterns were indicated by Metabolite Set Enrichment Analysis (MSEA). We identified metabolic rewiring networks, including the suppression of the oxidative pentose pathway and found that the normal tricarboxylic acid (TCA) cycle were decoupled from increases in glycolysis and glutamine reductive carboxylation. Well-established associated effects on nucleotide, amino acid and thiol metabolism were also seen. Novel aspects in SCC tissue were increased in Vitamin B complex cofactors, serotonin and a reduction of γ-aminobutyric acid (GABA). Our results show the value of FIE-HRMS as a high throughput screening method that could be exploited in clinical contexts. View Full-Text
Keywords: lung squamous cell carcinoma; flow infusion electrospray ionization high resolution mass spectrometry; untargeted metabolites; pathways lung squamous cell carcinoma; flow infusion electrospray ionization high resolution mass spectrometry; untargeted metabolites; pathways
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Paes de Araújo, R.; Bertoni, N.; Seneda, A.L.; Felix, T.F.; Carvalho, M.; Lewis, K.E.; Hasimoto, É.N.; Beckmann, M.; Drigo, S.A.; Reis, P.P.; Mur, L.A.J. Defining Metabolic Rewiring in Lung Squamous Cell Carcinoma. Metabolites 2019, 9, 47.

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